In recent years, as a consequence of an aging society, there has been an increase in the number of patients needing a care giver, such as patients who suffer from dementia, brain diseases, Parkinson's disease and the like. Such patients may forget to take their own medicine, or may have difficulty in taking medicine because of difficulty in swallowing. Thus, it is difficult for those patients to manage the medicine-taking activity by themselves. Therefore, there is a demand for administrating methods other than peroral administration. Besides, with patients who are treated with anti-mental illness medicine, if their medicine stops working, symptoms appear immediately thereby obstructing their life. To avoid this, administration has to be repeated several times a day before the medicinal efficacy is lost. Frequent administration imposes a great burden on the patient. In view of the above, long-lasting, controlled-release preparations are highly desirable in all disease regions.
For the long-lasting, controlled-release preparation, there have been heretofore investigated preparations for subcutaneous administration or intramuscular administration, most of which are in the form of microspheres making use of polylactic acid-glycolic acid copolymer (PLGA). For instance, mention is made of a microcapsule preparation Leuplin (registered trademark) wherein leuprorelin serving as an anticancer is encapsulated in a crosslinked matrix of PLGA. It is known that with these microspheres based on PLGA, the drug is released immediately after administration (initial burst) and that the concentration of the drug in the blood quickly exceeds an effective concentration, thus raising concerns with side effects. In the case of using PLGA, a difficulty is involved in encapsulating a drug at a high concentration with a high efficiency. Additionally, a limitation is placed on a clinically administrable drug dosage, thus presenting a problem on an improvement in the amount of drug to be encapsulated. Moreover, in the case where PLGA is used, an organic solvent should be used in the course of the preparation step, in which the removal of the organic solvent from the resulting preparation is essential, and which will be often difficult to achieve in the manufacture on an industrial scale. In addition, it has been accepted that the use of PLGA results in an increase in local acidity associated with hydrolysis, which can cause a serious problem in that inflammation occurs in administration site.
Besides, some approaches have been made in which bupivacaine is encapsulated in a multilayer membrane liposome according to a remote loading method. In the document, no relationship between the particle diameter and the controlled-release properties has been disclosed, and no knowledge has been obtained of an optimum particle diameter in controlled-release preparations. In addition, the sustained release time disclosed therein cannot be said to be long-lasting, during which postoperative intense pain continuing over three to five days is enabled to be alleviated for a sufficient period of time. Thus, a problem is presented concerning the duration (Non-Patent Document 1, Non-Patent Document 2, and Patent Document 1). Moreover, a multivesicular liposome (MVL) has been developed as a lipid-based controlled-release drug carrier for local or systematic drug delivery (Patent Document 2). This does not yet ensure a satisfactory duration on a clinical basis, thus presenting a problem.    Patent Document 1: JP-T-2002-522470    Patent Document 2: JP-T-2001-522870    Non-Patent Document 1: Anesthesiology, 2004, Vol. 101, No. 1, pp. 133-137, by Gilbert J. Grant et al., entitled “A Novel Liposomal Bupivacaine Formulation to Produce Ultralong-Acting Analgesia”    Non-Patent Document 2: Anesthesia & Analgesia, 2010, Vol. 110, No. 4, pp. 1018-1023, by Elyad M. Davidson et al., entitled “High-Dose Bupivacaine Remotely Loaded into Multivesicular Liposomes Demonstrates Slow Drug Release Without Systemic Toxic Plasma Concentrations After Subcutaneous Administration in Humans”